Trial Outcomes & Findings for Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions (NCT NCT02265341)

Last Updated: 2020-11-25

Results Overview

A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. Complete Response (CR): All of the following must be true:a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 10 months of treatment

Results posted on

2020-11-25

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Ponatinib Hydrochloride) Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ponatinib Hydrochloride) n=12 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	48.5 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
ECOG Performance Status 0	3 Participants n=5 Participants
ECOG Performance Status 1	7 Participants n=5 Participants
ECOG Performance Status 2	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 months of treatment

Population: Only patients who received treatment for at least 8 weeks are evaluable for this outcome (i.e. one patient refused further treatment and was therefore unevaluable for response at 8 weeks)

Outcome measures

Outcome measures
Measure	Treatment (Ponatinib Hydrochloride) n=11 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)	45.5 percentage of patients Interval 16.8 to 76.6

SECONDARY outcome

Timeframe: Up to 10 months of treatment

Population: Only patients who had baseline and subsequent CA 19-9 levels measured in the study are evaluable for this analysis.

This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a \>= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.

Outcome measures

Outcome measures
Measure	Treatment (Ponatinib Hydrochloride) n=3 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CA 19-9 Response	0 percentage of patients

SECONDARY outcome

Timeframe: Up to 10 months of treatment

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Outcome measures

Outcome measures
Measure	Treatment (Ponatinib Hydrochloride) n=12 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)	41.7 percentage of patients

SECONDARY outcome

Timeframe: Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.

Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Treatment (Ponatinib Hydrochloride) n=12 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	2.4 months Interval 1.9 to 9.2

SECONDARY outcome

Timeframe: Time from registration to death due to any cause, assessed up to a maximum of 3.3 years

Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Treatment (Ponatinib Hydrochloride) n=12 Participants Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Survival Time	15.7 months Interval 6.1 to The 95% Confidence interval upper limit was not able to be estimated due to an insufficient number of participants with events.

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to a maximum follow-up of 3.3 years

The Uniscale assessment of overall quality of life will be used. The Was It Worth It questionnaire will determine patient's satisfaction with the study. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means will be interpreted using Cohen's (1988) cut-offs. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to a maximum follow-up of 3.3 years

Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to a maximum follow-up of 3.3 years

Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Ponatinib Hydrochloride)

Serious events: 5 serious events

Other events: 11 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ponatinib Hydrochloride) n=12 participants at risk Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Pancreatitis	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Infections and infestations Sepsis	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.

Other adverse events

Other adverse events
Measure	Treatment (Ponatinib Hydrochloride) n=12 participants at risk Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Abdominal pain	58.3% 7/12 • Number of events 17 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Constipation	58.3% 7/12 • Number of events 21 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Diarrhea	25.0% 3/12 • Number of events 7 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Nausea	50.0% 6/12 • Number of events 18 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Vomiting	16.7% 2/12 • Number of events 5 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
General disorders Edema limbs	41.7% 5/12 • Number of events 11 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
General disorders Fatigue	75.0% 9/12 • Number of events 41 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
General disorders Fever	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Alanine aminotransferase increased	16.7% 2/12 • Number of events 3 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Alkaline phosphatase increased	33.3% 4/12 • Number of events 8 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Blood bilirubin increased	8.3% 1/12 • Number of events 2 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations CD4 lymphocytes decreased	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Lymphocyte count decreased	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Neutrophil count decreased	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations Platelet count decreased	41.7% 5/12 • Number of events 22 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Investigations White blood cell decreased	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Metabolism and nutrition disorders Anorexia	16.7% 2/12 • Number of events 2 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Metabolism and nutrition disorders Hyperglycemia	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Musculoskeletal and connective tissue disorders Back pain	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Nervous system disorders Headache	8.3% 1/12 • Number of events 2 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 2/12 • Number of events 3 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Hoarseness	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Skin and subcutaneous tissue disorders Dry skin	8.3% 1/12 • Number of events 1 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Skin and subcutaneous tissue disorders Rash maculo-papular	58.3% 7/12 • Number of events 21 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Vascular disorders Hypertension	25.0% 3/12 • Number of events 6 • Up to a maximum of 10 months on treatment. Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.

Additional Information

Mitesh J. Borad, MD

Mayo Clinic

Phone: 480/301-8335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place